Primary cilia and cancer: History
View Latest Version
Please note this is an old version of this entry, which may differ significantly from the current revision.
Subjects: Oncology
Contributor:
Takashi Shiromizu
,
Mizuki Yuge
,
Kousuke Kasahara
,
Daishi Yamakawa
,
Takaaki Matsui
,
Yasumasa Bessho
,
Masaki Inagaki
,
Yuhei Nishimura

Primacy cilia are antenna-like structures present in many vertebrate cells. These organelles detect extracellular cues, transduce signals into the cell, and play an essential role in ensuring correct cell proliferation, migration, and differentiation in a spatiotemporal manner. Not surprisingly, dysregulation of primary cilia can cause various diseases, including cancer. The structure and function of primary cilia are dynamically regulated through many proteins and various posttranslational mechanisms of these proteins, including phosphorylation, acetylation, and ubiquitination. Targeting these signaling that regulates the assembly and disassembly of primary cilia may be a promising approach for cancer treatment.

  • primary cilia
  • cancer
  • proliferation
  • ubiquitin ligase
  • deubiquitinase
  • protein-protein interaction
  • post-translational modification
  • migration
  • differentiation

1. Introduction

Primary cilia are antenna-like structures, 1–10 mm in length, that are present in a variety of vertebrate cells [1][2][3][4][5][6][7]. Primary cilia contain receptors and channels that detect signals from extracellular cues, such as mechanical flow and chemical stimulation, and transduce them into the cell, where they contribute to the maintenance of proper development and homeostasis. Considering these functions, it is not surprising that dysregulation of primary cilia function can cause cancer and other diseases, including ciliopathies, which manifest as various disease phenotypes such as congenital anomalies, neurodevelopmental disorders, and obesity [1][6][7][8][9][10].

The structure and function of primary cilia are dynamically and precisely regulated, enabling cells to proliferate, migrate, and differentiate in a spatiotemporally controlled manner [6][7][11]. The primary cilium is composed of three compartments: the basal body, the transition zone, and the axoneme [2]. The basal body is derived from the mother centriole. Both centrioles and basal body contain nine circularly arranged triplets of microtubules (A-, B-, and C-tubules). The axoneme consists of nine microtubule doublets projected from the A- and B-tubules of basal body. In contrast to motile cilia, a central pair of singlet microtubule is absent (+0) in primary cilia [12][13][14][15]. Therefore, the axoneme of primary cilia is described as 9´2+0. The transition zone is a short area located above the basal body characterized by Y-shaped fibers connecting the microtubule doublets to the ciliary membrane [16].

Primary cilia are disassembled and assembled when cells enter mitosis and exit the cell cycle, respectively [17][18][19]. The formation of primary cilia starts with the binding of small cytoplasmic vesicles transported from the Golgi apparatus to the mother centriole and conversion from the mother centriole to the basal body. The basal body is then moved and anchored to the plasma membrane. Coiled-coil protein 110, a component of the inhibitory complex of ciliogenesis, is removed to initiate axoneme elongation [20][21]. The ciliary vesicle then fuses with the plasma membrane, and large amounts of tubulin are transported from the cytoplasm into the cilium to extend the axoneme [22]. Many signaling molecules are also transported from the cytoplasm into the cilium (anterograde) and from the cilium into the cytoplasm (retrograde) by kinesin and dynein, respectively, which are motor proteins that travel along the axoneme [23].

Various types of posttranslational modification, including phosphorylation, acetylation, and ubiquitination, are involved in the dynamic regulation of the structure and function of cilia [2][4][5][6][7][24]. Modification of proteins by attachment of ubiquitin, a highly conserved 76-amino acid protein, is a critical step in targeting the selective degradation of proteins by proteasomes as part of the ubiquitin–proteasome system (UPS) [25]. Protein ubiquitination occurs in three steps. First, ubiquitin-activating enzymes (E1) bind to ubiquitin, which is expressed in all cell types; second, ubiquitin is transferred from E1 enzymes to ubiquitin-conjugating enzymes (E2); and finally, ubiquitin-ligating enzymes (E3) transfer the ubiquitin from E2 enzymes and ligate it to lysine residues on the target protein. To date, 2, approximately 40, and about 600 E1, E2, and E3 enzymes, respectively, have been identified in humans [25]. The selectivity of target protein ubiquitination is conferred by the combination of E2 and E3 enzymes. Protein ubiquitination is counteracted by deubiquitinase (DUB)-mediated removal of ubiquitin moieties from ubiquitinated proteins [26]. About 100 DUBs have been identified in humans. The balance between ubiquitination and deubiquitination of target proteins and their proteasomal degradation are tightly regulated processes, and dysregulation of the UPS has been detected in various disorders [27][28][29]. Several lines of evidence support a major role for the UPS in regulating the structure and function of cilia [4][5][6][7][30][31][32][33][34], suggest that the proteins involved in the assemble and disassemble of primary cilia through UPS may serve as novel therapeutic targets for the development of treatments for cancer and other disorders related to the dysregulation of primary cilia [7].

 

2. Roles of primary cilia in cancer

Primary cilia in cultured mouse 3T3 fibroblasts and human retinal pigment epithelial (RPE1) cells can be disassembled and assembled by serum stimulation and deprivation, respectively [17][18][35]. Aurora A kinase (AURKA), one of the most important mitotic kinases for cell-cycle control [36], plays important roles in deciliation by serum stimulation [37][38]. AURKA is activated by serum stimulation through Ca2+/calmodulin signaling, the non-canonical WNT pathway, and phosphatidylinositol signaling [38][39][40][41]. Serum stimulation also activates AURKA through the pathway involving epidermal growth factor receptor (EGFR), ubiquitin specific peptidase 8 (USP8), and trichoplein (TCHP) (described in the next section) [32][33][42]. Activated AURKA phosphorylates itself and target proteins during G1 phase, which stimulates the disassembly of primary cilia [38]. Several proteins associated with AURKA and ciliogenesis have been identified, including histone deacetylase 6 [35] and nudE neurodevelopment protein 1 (NDE1) [43]. In response to serum stimulation, NDE1 localizes at the basal body and suppresses ciliogenesis by tethering dynein light chain 1 [44]. Under serum deprivation conditions, cyclin-dependent kinase 5 is activated and phosphorylates NDE1. Phosphorylated NDE1 is then recognized and ubiquitylated by the E3 ligase complex SCFFBXW7, resulting in ciliogenesis [45][46]. Importantly, forced ciliation in cells growing under serum stimulation conditions can cause cell-cycle arrest [32][33][42][43][47]. These findings suggest that the primary cilium can act as a negative regulator of the cell cycle and may be a tumor suppressor organelle [3][4][5][6][7][10][48][49][50]. In fact, suppression of primary cilia function is associated with tumorigenesis, cell proliferation, and metastasis in many cancers, including glioblastoma [51], esophageal cancer [52], colon cancer [53], cholangiocarcinoma [54][55], pancreatic ductal adenocarcinoma [56], clear cell renal carcinoma [57], prostate cancer [58], ovarian cancer [59][60], melanoma [61], and chondrosarcoma [62] (Table 1). However, primary cilia can promote tumor progression under certain conditions. In medulloblastoma and basal cell skin carcinoma caused by gain-of-function mutation of SMO, primary cilia convert the GLI transcription factors GLI2 and GLI3 to their activated forms, inducing their translocation to the nucleus, increased transcription of Hedgehog target genes, and promotion of cell proliferation [63][64]. In contrast, primary cilia of medulloblastoma and basal cell skin carcinoma caused by gain-of-function mutation of GLI2 increases the activity of GLI3 as a transcriptional repressor, resulting in suppression of proliferation of these cancer cells [63][64]. Further work will thus be necessary to fully understand the context-dependent roles of primary cilia in cell proliferation.

 

Table 1. The roles of primary cilia in cancer.

Cancer cell

The role of primary cilia (PC) in the cancer

References

Glioblastoma

Inhibition of HDAC6 restores the loss of PC and suppressed the proliferation.

[51]

Esophageal squamous cell carcinoma

Knockdown (KD) of PRDX1 restores the loss of PC and suppressed the proliferation.

[52]

Colon cancer

Knockout of TTLL3 causes the loss of PC and promotes tumorigenesis in colon.

[53]

Cholangiocarcinoma

The number of PC is frequently reduced. Inhibition of HDAC6 restores the loss of PC and suppressed the proliferation

[54][55]

Pancreatic ductal adenocarcinoma

Inhibition of HDAC2 in Panc1 induces ciliogenesis and suppressed the proliferation.

[56]

Clear cell renal carcinoma

PC is lost by inactivation of VHL tumor suppressor.

[57]

Prostate cancer

KD of TACC3 restores the loss of PC and suppressed the proliferation.

[58]

Epithelial ovarian cancer

The number of PC is reduced, which is associated with centrosomal localization of AURKA. KD of AURKA restores the loss of PC and suppressed the oncogenic hedgehog signaling.

[59][60]

Melanoma

Deconstruction of PC is sufficient to drive metastatic formation.

[60]

Chondrosarcoma

Inhibition of HDAC6 restores the loss of PC and suppressed the proliferation.

[62]

Medulloblastoma, basal cell carcinoma

 

 

with GOF mutation of SMO

PC increase transcriptional activator and stimulate proliferation

[63][64]

with GOF mutation of GLI2

PC increase transcriptional suppressor and inhibit proliferation

[63][64]

 

This entry is adapted from the peer-reviewed paper 10.3390/ijms21175962

References

  1. Anvarian, Z.; Mykytyn, K.; Mukhopadhyay, S.; Pedersen, L. B.; Christensen, S. T., Cellular signalling by primary cilia in development, organ function and disease. Nature reviews. Nephrology 2019, 15, (4), 199-219.
  2. Malicki, J. J.; Johnson, C. A., The Cilium: Cellular Antenna and Central Processing Unit. Trends in cell biology 2017, 27, (2), 126-140.
  3. Goto, H.; Inoko, A.; Inagaki, M., Cell cycle progression by the repression of primary cilia formation in proliferating cells. Cellular and molecular life sciences : CMLS 2013, 70, (20), 3893-905.
  4. Izawa, I.; Goto, H.; Kasahara, K.; Inagaki, M., Current topics of functional links between primary cilia and cell cycle. Cilia 2015, 4, 12.
  5. Goto, H.; Inaba, H.; Inagaki, M., Mechanisms of ciliogenesis suppression in dividing cells. Cellular and molecular life sciences : CMLS 2017, 74, (5), 881-890.
  6. Nishimura, Y.; Kasahara, K.; Shiromizu, T.; Watanabe, M.; Inagaki, M., Primary cilia as signaling hubs in health and disease. Adv Sci (Weinh) 2019, 6, (1), 1801138.
  7. Shiromizu, T.; Yuge, M.; Kasahara, K.; Yamakawa, D.; Matsui, T.; Bessho, Y.; Inagaki, M.; Nishimura, Y., Targeting E3 Ubiquitin Ligases and Deubiquitinases in Ciliopathy and Cancer. International Journal of Molecular Sciences 2020, 21, (17), 5962.
  8. Valente, E. M.; Rosti, R. O.; Gibbs, E.; Gleeson, J. G., Primary cilia in neurodevelopmental disorders. Nat Rev Neurol 2014, 10, (1), 27-36.
  9. Reiter, J. F.; Leroux, M. R., Genes and molecular pathways underpinning ciliopathies. Nature reviews. Molecular cell biology 2017, 18, (9), 533-547.
  10. Liu, H.; Kiseleva, A. A.; Golemis, E. A., Ciliary signalling in cancer. Nat Rev Cancer 2018, 18, (8), 511-524.
  11. Wang, L.; Dynlacht, B. D., The regulation of cilium assembly and disassembly in development and disease. Development (Cambridge, England) 2018, 145, (18).
  12. Silverman, M. A.; Leroux, M. R., Intraflagellar transport and the generation of dynamic, structurally and functionally diverse cilia. Trends in cell biology 2009, 19, (7), 306-316.
  13. Loreng, T. D.; Smith, E. F., The Central Apparatus of Cilia and Eukaryotic Flagella. Cold Spring Harbor perspectives in biology 2017, 9, (2).
  14. Ishikawa, T., Axoneme Structure from Motile Cilia. Cold Spring Harbor perspectives in biology 2017, 9, (1).
  15. Mitchison, H. M.; Valente, E. M., Motile and non-motile cilia in human pathology: from function to phenotypes. The Journal of pathology 2017, 241, (2), 294-309.
  16. Reiter, J. F.; Blacque, O. E.; Leroux, M. R., The base of the cilium: roles for transition fibres and the transition zone in ciliary formation, maintenance and compartmentalization. EMBO Rep 2012, 13, (7), 608-18.
  17. Tucker, R. W.; Pardee, A. B.; Fujiwara, K., Centriole ciliation is related to quiescence and DNA synthesis in 3T3 cells. Cell 1979, 17, (3), 527-35.
  18. Tucker, R. W.; Scher, C. D.; Stiles, C. D., Centriole deciliation associated with the early response of 3T3 cells to growth factors but not to SV40. Cell 1979, 18, (4), 1065-72.
  19. Rieder, C. L.; Jensen, C. G.; Jensen, L. C. W., The resorption of primary cilia during mitosis in a vertebrate (PtK1) cell line. Journal of Ultrastructure Research 1979, 68, (2), 173-185.
  20. Tsang, W. Y.; Dynlacht, B. D., CP110 and its network of partners coordinately regulate cilia assembly. Cilia 2013, 2, (1), 9.
  21. Yadav, S. P.; Sharma, N. K.; Liu, C.; Dong, L.; Li, T.; Swaroop, A., Centrosomal protein CP110 controls maturation of the mother centriole during cilia biogenesis. Development (Cambridge, England) 2016, 143, (9), 1491-501.
  22. Craft, J. M.; Harris, J. A.; Hyman, S.; Kner, P.; Lechtreck, K. F., Tubulin transport by IFT is upregulated during ciliary growth by a cilium-autonomous mechanism. The Journal of cell biology 2015, 208, (2), 223-37.
  23. Malicki, J.; Avidor-Reiss, T., From the cytoplasm into the cilium: bon voyage. Organogenesis 2014, 10, (1), 138-57.
  24. Mirvis, M.; Stearns, T.; James Nelson, W., Cilium structure, assembly, and disassembly regulated by the cytoskeleton. Biochem J 2018, 475, (14), 2329-2353.
  25. Clague, M. J.; Heride, C.; Urbé, S., The demographics of the ubiquitin system. Trends in cell biology 2015, 25, (7), 417-26.
  26. Leznicki, P.; Kulathu, Y., Mechanisms of regulation and diversification of deubiquitylating enzyme function. Journal of cell science 2017, 130, (12), 1997-2006.
  27. Popovic, D.; Vucic, D.; Dikic, I., Ubiquitination in disease pathogenesis and treatment. Nature medicine 2014, 20, (11), 1242-53.
  28. Harrigan, J. A.; Jacq, X.; Martin, N. M.; Jackson, S. P., Deubiquitylating enzymes and drug discovery: emerging opportunities. Nature reviews. Drug discovery 2018, 17, (1), 57-78.
  29. Senft, D.; Qi, J.; Ronai, Z. A., Ubiquitin ligases in oncogenic transformation and cancer therapy. Nat Rev Cancer 2018, 18, (2), 69-88.
  30. Shearer, R. F.; Saunders, D. N., Regulation of primary cilia formation by the ubiquitin-proteasome system. Biochem Soc Trans 2016, 44, (5), 1265-1271.
  31. Hossain, D.; Tsang, W. Y., The role of ubiquitination in the regulation of primary cilia assembly and disassembly. Seminars in cell & developmental biology 2019, 93, 145-152.
  32. Kasahara, K.; Kawakami, Y.; Kiyono, T.; Yonemura, S.; Kawamura, Y.; Era, S.; Matsuzaki, F.; Goshima, N.; Inagaki, M., Ubiquitin-proteasome system controls ciliogenesis at the initial step of axoneme extension. Nat Commun 2014, 5, 5081.
  33. Kasahara, K.; Aoki, H.; Kiyono, T.; Wang, S.; Kagiwada, H.; Yuge, M.; Tanaka, T.; Nishimura, Y.; Mizoguchi, A.; Goshima, N.; Inagaki, M., EGF receptor kinase suppresses ciliogenesis through activation of USP8 deubiquitinase. Nat Commun 2018, 9, (1), 758.
  34. Toulis, V.; Marfany, G., By the Tips of Your Cilia: Ciliogenesis in the Retina and the Ubiquitin-Proteasome System. Adv Exp Med Biol 2020, 1233, 303-310.
  35. Pugacheva, E. N.; Jablonski, S. A.; Hartman, T. R.; Henske, E. P.; Golemis, E. A., HEF1-dependent Aurora A activation induces disassembly of the primary cilium. Cell 2007, 129, (7), 1351-63.
  36. Otto, T.; Sicinski, P., Cell cycle proteins as promising targets in cancer therapy. Nat Rev Cancer 2017, 17, (2), 93-115.
  37. Liang, Y.; Meng, D.; Zhu, B.; Pan, J., Mechanism of ciliary disassembly. Cellular and molecular life sciences : CMLS 2016, 73, (9), 1787-802.
  38. Korobeynikov, V.; Deneka, A. Y.; Golemis, E. A., Mechanisms for nonmitotic activation of Aurora-A at cilia. Biochem Soc Trans 2017, 45, (1), 37-49.
  39. Plotnikova, O. V.; Nikonova, A. S.; Loskutov, Y. V.; Kozyulina, P. Y.; Pugacheva, E. N.; Golemis, E. A., Calmodulin activation of Aurora-A kinase (AURKA) is required during ciliary disassembly and in mitosis. Molecular biology of the cell 2012, 23, (14), 2658-70.
  40. Lee, K. H.; Johmura, Y.; Yu, L. R.; Park, J. E.; Gao, Y.; Bang, J. K.; Zhou, M.; Veenstra, T. D.; Yeon Kim, B.; Lee, K. S., Identification of a novel Wnt5a-CK1varepsilon-Dvl2-Plk1-mediated primary cilia disassembly pathway. The EMBO journal 2012, 31, (14), 3104-17.
  41. Plotnikova, O. V.; Seo, S.; Cottle, D. L.; Conduit, S.; Hakim, S.; Dyson, J. M.; Mitchell, C. A.; Smyth, I. M., INPP5E interacts with AURKA, linking phosphoinositide signaling to primary cilium stability. Journal of cell science 2015, 128, (2), 364-72.
  42. Inoko, A.; Matsuyama, M.; Goto, H.; Ohmuro-Matsuyama, Y.; Hayashi, Y.; Enomoto, M.; Ibi, M.; Urano, T.; Yonemura, S.; Kiyono, T.; Izawa, I.; Inagaki, M., Trichoplein and Aurora A block aberrant primary cilia assembly in proliferating cells. The Journal of cell biology 2012, 197, (3), 391-405.
  43. Gabriel, E.; Wason, A.; Ramani, A.; Gooi, L. M.; Keller, P.; Pozniakovsky, A.; Poser, I.; Noack, F.; Telugu, N. S.; Calegari, F.; Saric, T.; Hescheler, J.; Hyman, A. A.; Gottardo, M.; Callaini, G.; Alkuraya, F. S.; Gopalakrishnan, J., CPAP promotes timely cilium disassembly to maintain neural progenitor pool. The EMBO journal 2016, 35, (8), 803-19.
  44. Pazour, G. J.; Wilkerson, C. G.; Witman, G. B., A dynein light chain is essential for the retrograde particle movement of intraflagellar transport (IFT). The Journal of cell biology 1998, 141, (4), 979-92.
  45. Maskey, D.; Marlin, M. C.; Kim, S.; Kim, S.; Ong, E. C.; Li, G.; Tsiokas, L., Cell cycle-dependent ubiquitylation and destruction of NDE1 by CDK5-FBW7 regulates ciliary length. The EMBO journal 2015, 34, (19), 2424-40.
  46. Nikonova, A. S.; Golemis, E. A., The tumor suppressor FBW7 controls ciliary length. The EMBO journal 2015, 34, (19), 2388-90.
  47. Inaba, H.; Goto, H.; Kasahara, K.; Kumamoto, K.; Yonemura, S.; Inoko, A.; Yamano, S.; Wanibuchi, H.; He, D.; Goshima, N.; Kiyono, T.; Hirotsune, S.; Inagaki, M., Ndel1 suppresses ciliogenesis in proliferating cells by regulating the trichoplein-Aurora A pathway. The Journal of cell biology 2016, 212, (4), 409-23.
  48. Fabbri, L.; Bost, F.; Mazure, N. M., Primary Cilium in Cancer Hallmarks. Int J Mol Sci 2019, 20, (6).
  49. Higgins, M.; Obaidi, I.; McMorrow, T., Primary cilia and their role in cancer. Oncol Lett 2019, 17, (3), 3041-3047.
  50. Peixoto, E.; Richard, S.; Pant, K.; Biswas, A.; Gradilone, S. A., The primary cilium: Its role as a tumor suppressor organelle. Biochem Pharmacol 2020, 175, 113906.
  51. Urdiciain, A.; Erausquin, E.; Meléndez, B.; Rey, J. A.; Idoate, M. A.; Castresana, J. S., Tubastatin A, an inhibitor of HDAC6, enhances temozolomide‑induced apoptosis and reverses the malignant phenotype of glioblastoma cells. Int J Oncol 2019, 54, (5), 1797-1808.
  52. Chen, Q.; Li, J.; Yang, X.; Ma, J.; Gong, F.; Liu, Y., Prdx1 promotes the loss of primary cilia in esophageal squamous cell carcinoma. BMC Cancer 2020, 20, (1), 372.
  53. Rocha, C.; Papon, L.; Cacheux, W.; Marques Sousa, P.; Lascano, V.; Tort, O.; Giordano, T.; Vacher, S.; Lemmers, B.; Mariani, P.; Meseure, D.; Medema, J. P.; Bieche, I.; Hahne, M.; Janke, C., Tubulin glycylases are required for primary cilia, control of cell proliferation and tumor development in colon. The EMBO journal 2014, 33, (19), 2247-60.
  54. Gradilone, S. A.; Radtke, B. N.; Bogert, P. S.; Huang, B. Q.; Gajdos, G. B.; LaRusso, N. F., HDAC6 inhibition restores ciliary expression and decreases tumor growth. Cancer research 2013, 73, (7), 2259-70.
  55. Mansini, A. P.; Peixoto, E.; Thelen, K. M.; Gaspari, C.; Jin, S.; Gradilone, S. A., The cholangiocyte primary cilium in health and disease. Biochimica et biophysica acta 2018, 1864, (4 Pt B), 1245-1253.
  56. Kobayashi, T.; Nakazono, K.; Tokuda, M.; Mashima, Y.; Dynlacht, B. D.; Itoh, H., HDAC2 promotes loss of primary cilia in pancreatic ductal adenocarcinoma. EMBO Rep 2017, 18, (2), 334-343.
  57. Esteban, M. A.; Harten, S. K.; Tran, M. G.; Maxwell, P. H., Formation of primary cilia in the renal epithelium is regulated by the von Hippel-Lindau tumor suppressor protein. J Am Soc Nephrol 2006, 17, (7), 1801-6.
  58. Qie, Y.; Wang, L.; Du, E.; Chen, S.; Lu, C.; Ding, N.; Yang, K.; Xu, Y., TACC3 promotes prostate cancer cell proliferation and restrains primary cilium formation. Experimental cell research 2020, 390, (2), 111952.
  59. Bhattacharya, R.; Kwon, J.; Ali, B.; Wang, E.; Patra, S.; Shridhar, V.; Mukherjee, P., Role of hedgehog signaling in ovarian cancer. Clin Cancer Res 2008, 14, (23), 7659-66.
  60. Egeberg, D. L.; Lethan, M.; Manguso, R.; Schneider, L.; Awan, A.; Jorgensen, T. S.; Byskov, A. G.; Pedersen, L. B.; Christensen, S. T., Primary cilia and aberrant cell signaling in epithelial ovarian cancer. Cilia 2012, 1, (1), 15.
  61. Zingg, D.; Debbache, J.; Peña-Hernández, R.; Antunes, A. T.; Schaefer, S. M.; Cheng, P. F.; Zimmerli, D.; Haeusel, J.; Calçada, R. R.; Tuncer, E.; Zhang, Y.; Bossart, R.; Wong, K. K.; Basler, K.; Dummer, R.; Santoro, R.; Levesque, M. P.; Sommer, L., EZH2-Mediated Primary Cilium Deconstruction Drives Metastatic Melanoma Formation. Cancer Cell 2018, 34, (1), 69-84.e14.
  62. Xiang, W.; Guo, F.; Cheng, W.; Zhang, J.; Huang, J.; Wang, R.; Ma, Z.; Xu, K., HDAC6 inhibition suppresses chondrosarcoma by restoring the expression of primary cilia. Oncol Rep 2017, 38, (1), 229-236.
  63. Wong, S. Y.; Seol, A. D.; So, P. L.; Ermilov, A. N.; Bichakjian, C. K.; Epstein, E. H., Jr.; Dlugosz, A. A.; Reiter, J. F., Primary cilia can both mediate and suppress Hedgehog pathway-dependent tumorigenesis. Nature medicine 2009, 15, (9), 1055-61.
  64. Han, Y. G.; Kim, H. J.; Dlugosz, A. A.; Ellison, D. W.; Gilbertson, R. J.; Alvarez-Buylla, A., Dual and opposing roles of primary cilia in medulloblastoma development. Nature medicine 2009, 15, (9), 1062-5.
More
© Text is available under the terms and conditions of the Creative Commons Attribution (CC BY) license; additional terms may apply. By using this site, you agree to the Terms and Conditions and Privacy Policy.
This entry is offline, you can click here to edit this entry!
ScholarVision Creations
Feedback